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Tissue deposits (Tissue
Accumulations)
By
Dr/ Rana “M. ElSaid” Abou-ElFetouh Abdalla
Lecturer of pathology
MD., DipRCPath
Pathology Department.
Official email: rana.elsaied@fmed.bu.edu.eg
Instructor information
Dr/ Rana “M. ElSaid” Abou-ElFetouh Abdalla
Lecturer of pathology
MD., DipRCPath
Pathology Department.
Official email: rana.elsaied@fmed.bu.edu.eg
Learning
Outcomes
By the end of the lecture, the students will be able to:
1- classify tissue accumulations.
2-outline the difference between endogenous and
Exogenous pigmentation.
3-highlight the difference between types of abnormal
calcification (Dystrophic calcification, metastatic
calcification)
4- explain the pathogensis of heamochromatosis
5-Identify the different types of amyloidosis
(classification), the causes of its deposition and its
distribution in the different body organs
Case
• Mrs Lamiaa, a 40-year old female patient,
came to the clinic c/o lower limp swelling and
SOB on exertion gradually increasing over the
past 2 months.
• The medical records revealed that she was
diagnosed with Mediterranean-sea fever 10
years ago. She reported neglecting her
medications and reported obvious decrease in
her urine output.
• On examination, generalized edema was
observed. Renal function tests were requested
and came up altered.
• Renal biopsy was ordered.
Tissue deposits
Intracellular
Metabolic derangements
lead to accumulation of
different substances in
the cytoplasm or in
organelles or in nucleus
Extracellular
• Deposition of insoluble
substance in the
extracellular matrix
Intracellular deposits
lipid
•Fatty change
•Atherosclerosis
•Cholesterlosis
•xanthoma
protein
• intracellular
hyalinosis
carbohydrates
•Mucoid
degeneration
Pigments
•exogenous
•Endogenous
Calcium
•metastatic
•dystrophic
extracellular deposits
proteins
• Connective tissue
hyalinosis (spleen-
kidney- prostate)
carbohydrates
• Myxomatous
changes (Myxedema-
Myxoid deg.)
Amyloid
• Generalized
• Localized
I- Lipids
A- neutral fat
• Fatty change
B-cholesterol
• Atherosclerosis (intima of blood vs)
• Xanthomas (skin and subcutanous tissues)
• Cholesterosis (gall bladder)
II-Protein deposition (hyalinosis)
Definition: It is alterations of intracellular proteins to
appear as cytoplasmic homogenous rounded eosinophilic
globules in hematoxyline and eosin stained sections.
Examples:
1. Russell’s bodies: In a disease named Rhinoscleroma
(intracellular)
2. In proximal convoluted tubules of the kidney: In cases
of proteinuria.(intra & extra cellular)
3. Mallory bodies: in alcoholic cirrhosis (intracellular).
III- Carbohydrates
A- Glycogen
a group of diseases
called glycogen storage
diseases.
Etiology: due to abnormal
glycogen metabolism
Microscopically: the cells
are swollen with clear
cytoplasmic vacuoles
B. Mucin (Mucoid or Mucinous
Degeneration):
mucin hypersecretion
Examples:Catarrhal
inflammation - Mucoid
carcinoma
Microscopically:
• cells distended with
mucin
• signet-ring cell-
• The cells may rupture
with release of mucin
(mucin lackes)
IV- pigments
exogenous
1-Inhalation :
• Anthracosis: carbon
• Silicosis: In cool miners,
silica
2-Injection : TattooingColored
dye (India ink)
3-Ingestion :
• Plumbism (lead poisoning
as a blue line on gums.
• Argyria (Silver poisoning):
Gray coloration of the skin,
endogenous
1- Melanin.
2- Lipofuscin.
3- Hemoglobin
(hemosiderin).
A-Melanin
• brown-black, pigment formed in melanocytes
• Melanin pigment disturbances may be hyper-
or hypopigmentation
Melanin
A- Hyperpigmentation
❖ Localized:
• Melanocytes tumors
• Café-au-lait spots
• Melanosis coli
• Chloasma
❖ generalized
• Prolonged exposure to
sunlight
• Addison’s disease
B- Hypopigmentation
❖ Localized
• Leucoderma
• Vetiligo
❖ Generalized
• Occulocutanous albinism
B- Lipofuscin pigment (Liopchrome
pigment
• Brown or yellow pigments
• particularly prominent in
the liver and heart of aging
patients
• not injurious to the cell or
its functions
• due to tear and wear →
Tissue breakdown →
Release of phospholipids →
Phagocytosed by the
healthy neighboring cells →
Intracellular accumulation
of lipofuscin pigment →
Brownish coloration.
c- Hemosiderin
a hemoglobin-derived, golden yellow to-brown, granular or
crystalline pigment derived from iron
• Local excesses of hemosiderin
• Common bruise
• Systemic overload of iron -
HEMOSIDEROSIS
❖ 1ry Hemochromatosis
(Bronzed Diabetes )
❖ 2ry Hemochromatosis
• Hemolytic anemias
• Repeated blood transfusions
V- Calcium
Pathologic calcification is the abnormal tissue deposition of calcium
salts, together with smaller amounts of iron, magnesium, and other
mineral salts
Types
❖ Dystrophic
• deposition occurs locally in dying tissues
• it occurs despite normal serum levels of calcium
• In absence of derangements in calcium metabolism
❖ Metastatic
• deposition of calcium salts in otherwise normal tissues
• results from hypercalcemia
• secondary to some disturbance in calcium metabolism.
❖ Calcinosis. Rare type of pathological calcification of
unknown cause.
❖ Stone formation. Calcium salts deposition in the cavities
of hollow organs as urinary and biliary tracts stone
Dystrophic calcification
➢ Degenerated or necrotic
tissue
➢ Examples
• in the atheromas of
advanced atherosclerosis
• develops in aging or damaged
heart valves
Metastatic calcification
Causes
• hyperparathyroidism
• Resorption of bone tissue e.g
➢ primary tumors of bone
marrow (e.g., multiple
myeloma
➢ diffuse skeletal metastasis
(e.g., breast cancer),
➢ accelerated bone turnover
(e.g., Paget disease)
➢ Immobilization
• Vitamin D–related disorders
• Renal failure
Compare between dystrophic and metastatic
calcification
Extracellular deposits
Amyloidosis
• Definition: Extracellular deposition of homogenous hyaline
eosinophilic amyloid material (abnormal protein).
Classification of amyloidosis:
❑ Localized
❑ Systemic (generalize)
I-1ry amyloidosis… immunocytic derived AL type
II-2ry amyloidosis… reactive amyloid (SAA)
III-Haemodialysis-associated amyloidosis (B2-microglobulin)
IV-Heredofamilial amyloidosis (Transthyretin)
Primary (AL)
➢ unknown etiology,
which may be due to:-
Colonal expansion of
immunocyte
proliferation
➢ Organs affected:
Myocardium – Intestine
- Esophagus - skin-
Peripheral nerves - May
be also in solid organs
as Kidney
Secondary (AA)
➢ due to:
• Chronic Inflammations.
• Autoimmune Diseases
• Malignant Tumor
➢ It particularly affects
the parenchymatous
organs as:
- Kidneys - Liver- Spleen -
Lymph nodes - May be
intestine and heart.
Haemodialysis associated
amyloidosis
• Occur in 70% of
patients with chronic
renal failure subjected
to chronic
hemodialysis.
• Deposition of B2-
microglobulin protein.
Heredofamilial amyloidos
• an inherited condition
that may be
characterized by
systemic or localized
deposition
of amyloid in body
tissues
• Mutant TTRs
• Ppt in nerves
Localized amyloidosis
a- Endocrine associated amyloidosis:
- In medullary carcinoma of thyroid
- In pancrease causing D.M
b- Senile amyloid :
➢In old age amyloid material (transthyretin)
may be deposited exatracellulary in between
cardiac muscle fibers.
➢In brain (Alzheimer’s disease)
Amyloidosis
Diagnosis
Tissue biopsy :
• Congo red ……..orange
• By polarized light
……apple green color
Treatment
• No treatment available
• Organ transplantation
Back to the case
• name the possible diagnosis
• Classify the disease in this case
• Name a stain could be useful in
confirming your diagnosis
• Describe the prognosis for
Summary
An 84-year-old man dies. At autopsy, his heart is
small and dark brown on sectioning.
Microscopically, there is light brown perinuclear
pigment Which of the following substances is
mostly the cause?
A Hemosiderin from iron overload
B Lipochrome from 'wear and tear'
C Glycogen from a storage disease
D Cholesterol from atherosclerosis
E Calcium deposition following necrosis
A 48-year-old woman has a malignant lymphoma. She is
treated with a chemotherapeutic agent which results in
the loss of individual neoplastic cells through
fragmentation of individual cell nuclei and cytoplasm.
Over the next 2 months, the lymphoma decreases in
size. By which of the following mechanisms has her
neoplasm primarily responded to therapy?
A Coagulative necrosis
B Mitochondrial poisoning
C Phagocytosis
D Acute inflammation
E Apoptosis
A 22 year-old woman has congenital anemia that
has required multiple transfusions of RBCs for many
years. Which of the following findings would most likely
appear in a liver biopsy specimen?
A. Steatosis in hepatocytes
B. Bilirubin in canaliculi
C. Glycogen in hepatocytes
D. Amyloid in the liver
E. Hemosiderin in hepatocytes
References & Resources
• https://www.clinicalkey.com/student/content/bo
ok/3-s2.0-B9781455726134000025#hl0001584
• https://www.clinicalkey.com/student/content/bo
ok/3-s2.0-B9781455726134000025#hl0001977
• https://www.clinicalkey.com/student/content/bo
ok/3-s2.0-B9781455726134000025#hl0002133
• https://youtu.be/P2rAeaR_zuY
• https://youtu.be/j962b8ZdU8w
pathology is art

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Tissue accumulation

  • 1. Tissue deposits (Tissue Accumulations) By Dr/ Rana “M. ElSaid” Abou-ElFetouh Abdalla Lecturer of pathology MD., DipRCPath Pathology Department. Official email: rana.elsaied@fmed.bu.edu.eg
  • 2. Instructor information Dr/ Rana “M. ElSaid” Abou-ElFetouh Abdalla Lecturer of pathology MD., DipRCPath Pathology Department. Official email: rana.elsaied@fmed.bu.edu.eg
  • 3. Learning Outcomes By the end of the lecture, the students will be able to: 1- classify tissue accumulations. 2-outline the difference between endogenous and Exogenous pigmentation. 3-highlight the difference between types of abnormal calcification (Dystrophic calcification, metastatic calcification) 4- explain the pathogensis of heamochromatosis 5-Identify the different types of amyloidosis (classification), the causes of its deposition and its distribution in the different body organs
  • 4. Case • Mrs Lamiaa, a 40-year old female patient, came to the clinic c/o lower limp swelling and SOB on exertion gradually increasing over the past 2 months. • The medical records revealed that she was diagnosed with Mediterranean-sea fever 10 years ago. She reported neglecting her medications and reported obvious decrease in her urine output. • On examination, generalized edema was observed. Renal function tests were requested and came up altered. • Renal biopsy was ordered.
  • 5. Tissue deposits Intracellular Metabolic derangements lead to accumulation of different substances in the cytoplasm or in organelles or in nucleus Extracellular • Deposition of insoluble substance in the extracellular matrix
  • 6. Intracellular deposits lipid •Fatty change •Atherosclerosis •Cholesterlosis •xanthoma protein • intracellular hyalinosis carbohydrates •Mucoid degeneration Pigments •exogenous •Endogenous Calcium •metastatic •dystrophic extracellular deposits proteins • Connective tissue hyalinosis (spleen- kidney- prostate) carbohydrates • Myxomatous changes (Myxedema- Myxoid deg.) Amyloid • Generalized • Localized
  • 7. I- Lipids A- neutral fat • Fatty change B-cholesterol • Atherosclerosis (intima of blood vs) • Xanthomas (skin and subcutanous tissues) • Cholesterosis (gall bladder)
  • 8. II-Protein deposition (hyalinosis) Definition: It is alterations of intracellular proteins to appear as cytoplasmic homogenous rounded eosinophilic globules in hematoxyline and eosin stained sections. Examples: 1. Russell’s bodies: In a disease named Rhinoscleroma (intracellular) 2. In proximal convoluted tubules of the kidney: In cases of proteinuria.(intra & extra cellular) 3. Mallory bodies: in alcoholic cirrhosis (intracellular).
  • 9. III- Carbohydrates A- Glycogen a group of diseases called glycogen storage diseases. Etiology: due to abnormal glycogen metabolism Microscopically: the cells are swollen with clear cytoplasmic vacuoles B. Mucin (Mucoid or Mucinous Degeneration): mucin hypersecretion Examples:Catarrhal inflammation - Mucoid carcinoma Microscopically: • cells distended with mucin • signet-ring cell- • The cells may rupture with release of mucin (mucin lackes)
  • 10. IV- pigments exogenous 1-Inhalation : • Anthracosis: carbon • Silicosis: In cool miners, silica 2-Injection : TattooingColored dye (India ink) 3-Ingestion : • Plumbism (lead poisoning as a blue line on gums. • Argyria (Silver poisoning): Gray coloration of the skin, endogenous 1- Melanin. 2- Lipofuscin. 3- Hemoglobin (hemosiderin).
  • 11. A-Melanin • brown-black, pigment formed in melanocytes • Melanin pigment disturbances may be hyper- or hypopigmentation
  • 12. Melanin A- Hyperpigmentation ❖ Localized: • Melanocytes tumors • Café-au-lait spots • Melanosis coli • Chloasma ❖ generalized • Prolonged exposure to sunlight • Addison’s disease B- Hypopigmentation ❖ Localized • Leucoderma • Vetiligo ❖ Generalized • Occulocutanous albinism
  • 13. B- Lipofuscin pigment (Liopchrome pigment • Brown or yellow pigments • particularly prominent in the liver and heart of aging patients • not injurious to the cell or its functions • due to tear and wear → Tissue breakdown → Release of phospholipids → Phagocytosed by the healthy neighboring cells → Intracellular accumulation of lipofuscin pigment → Brownish coloration.
  • 14. c- Hemosiderin a hemoglobin-derived, golden yellow to-brown, granular or crystalline pigment derived from iron • Local excesses of hemosiderin • Common bruise • Systemic overload of iron - HEMOSIDEROSIS ❖ 1ry Hemochromatosis (Bronzed Diabetes ) ❖ 2ry Hemochromatosis • Hemolytic anemias • Repeated blood transfusions
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  • 17. V- Calcium Pathologic calcification is the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salts
  • 18. Types ❖ Dystrophic • deposition occurs locally in dying tissues • it occurs despite normal serum levels of calcium • In absence of derangements in calcium metabolism ❖ Metastatic • deposition of calcium salts in otherwise normal tissues • results from hypercalcemia • secondary to some disturbance in calcium metabolism. ❖ Calcinosis. Rare type of pathological calcification of unknown cause. ❖ Stone formation. Calcium salts deposition in the cavities of hollow organs as urinary and biliary tracts stone
  • 19. Dystrophic calcification ➢ Degenerated or necrotic tissue ➢ Examples • in the atheromas of advanced atherosclerosis • develops in aging or damaged heart valves Metastatic calcification Causes • hyperparathyroidism • Resorption of bone tissue e.g ➢ primary tumors of bone marrow (e.g., multiple myeloma ➢ diffuse skeletal metastasis (e.g., breast cancer), ➢ accelerated bone turnover (e.g., Paget disease) ➢ Immobilization • Vitamin D–related disorders • Renal failure
  • 20. Compare between dystrophic and metastatic calcification
  • 22. Amyloidosis • Definition: Extracellular deposition of homogenous hyaline eosinophilic amyloid material (abnormal protein). Classification of amyloidosis: ❑ Localized ❑ Systemic (generalize) I-1ry amyloidosis… immunocytic derived AL type II-2ry amyloidosis… reactive amyloid (SAA) III-Haemodialysis-associated amyloidosis (B2-microglobulin) IV-Heredofamilial amyloidosis (Transthyretin)
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  • 25. Primary (AL) ➢ unknown etiology, which may be due to:- Colonal expansion of immunocyte proliferation ➢ Organs affected: Myocardium – Intestine - Esophagus - skin- Peripheral nerves - May be also in solid organs as Kidney Secondary (AA) ➢ due to: • Chronic Inflammations. • Autoimmune Diseases • Malignant Tumor ➢ It particularly affects the parenchymatous organs as: - Kidneys - Liver- Spleen - Lymph nodes - May be intestine and heart.
  • 26. Haemodialysis associated amyloidosis • Occur in 70% of patients with chronic renal failure subjected to chronic hemodialysis. • Deposition of B2- microglobulin protein. Heredofamilial amyloidos • an inherited condition that may be characterized by systemic or localized deposition of amyloid in body tissues • Mutant TTRs • Ppt in nerves
  • 27. Localized amyloidosis a- Endocrine associated amyloidosis: - In medullary carcinoma of thyroid - In pancrease causing D.M b- Senile amyloid : ➢In old age amyloid material (transthyretin) may be deposited exatracellulary in between cardiac muscle fibers. ➢In brain (Alzheimer’s disease)
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  • 29. Amyloidosis Diagnosis Tissue biopsy : • Congo red ……..orange • By polarized light ……apple green color Treatment • No treatment available • Organ transplantation
  • 30. Back to the case • name the possible diagnosis • Classify the disease in this case • Name a stain could be useful in confirming your diagnosis • Describe the prognosis for
  • 32. An 84-year-old man dies. At autopsy, his heart is small and dark brown on sectioning. Microscopically, there is light brown perinuclear pigment Which of the following substances is mostly the cause? A Hemosiderin from iron overload B Lipochrome from 'wear and tear' C Glycogen from a storage disease D Cholesterol from atherosclerosis E Calcium deposition following necrosis
  • 33. A 48-year-old woman has a malignant lymphoma. She is treated with a chemotherapeutic agent which results in the loss of individual neoplastic cells through fragmentation of individual cell nuclei and cytoplasm. Over the next 2 months, the lymphoma decreases in size. By which of the following mechanisms has her neoplasm primarily responded to therapy? A Coagulative necrosis B Mitochondrial poisoning C Phagocytosis D Acute inflammation E Apoptosis
  • 34. A 22 year-old woman has congenital anemia that has required multiple transfusions of RBCs for many years. Which of the following findings would most likely appear in a liver biopsy specimen? A. Steatosis in hepatocytes B. Bilirubin in canaliculi C. Glycogen in hepatocytes D. Amyloid in the liver E. Hemosiderin in hepatocytes
  • 35. References & Resources • https://www.clinicalkey.com/student/content/bo ok/3-s2.0-B9781455726134000025#hl0001584 • https://www.clinicalkey.com/student/content/bo ok/3-s2.0-B9781455726134000025#hl0001977 • https://www.clinicalkey.com/student/content/bo ok/3-s2.0-B9781455726134000025#hl0002133 • https://youtu.be/P2rAeaR_zuY • https://youtu.be/j962b8ZdU8w